Voiced by George Lowe, Space Ghost, whose real name is Tad Eustace Ghostal, was a superhero in the 60s. Though occasionally conflicted about whether saving the world or hosting a talk show best suits him, Tad genuinely wants to put on the best talk show he can. Unfortunately, his failings tend to get the better of him. He is childish, egotistical, and petty, and he remains generally oblivious to his surroundings. He has little regard for the well-being of others and often demeans his sidekicks and guests. In an interview with Conan O'Brien, Space Ghost announces that he has always been dead and was never a space man. "I was dead long before you were born, Conan, and I'll be dead long before you're dead".

Voiced by C. Martin Croker, Zorak is the band leader and a mantis-like alien, known for his hatred of Space Ghost. Extremely evil, he once ate his own nephew. He is a virgin, largely due to the fact that he does not wish to be eaten by his mate after intercourse, as is normal for mantises. He has no remorse, feels no pity and acts only to meet his own ends. He was Brak's childhood friend. His superhero persona is Batmantis. Though Space Ghost's prisoner, Zorak retains his membership in the Council of Doom. He claims he is either a locust or a mantis, but he often changes his mind. In episode 97, "Al", it is revealed that Mr. Pong (Allan Alcorn) is Zorak's father. He also co-hosted Cartoon Planet and currently hosts a revival of this series with Brak.

Voiced by C. Martin Croker, Moltar is the show's director and producer. His body is made entirely of lava, and he normally wears an orange and gray full-body containment suit which has a breathing receptacle. By far the most competent and level-headed character, Moltar sometimes tends to be smarter than he seems. He tends to be very good friends with Zorak, even though Zorak doesn't have the same feelings for him. He is a big fan of CHiPs and its star, Erik Estrada. In the original 1968 Space Ghost series, he was voiced by Don Messick, his name was spelled "Moltor" and his clothing was white and yellow.

Voiced by Andy Merrill, Brak is some sort of cat-like alien with large fangs who, although a villain, is the least threatening one on the program. He appeared on SGC2C periodically, often with the Council of Doom, of which he was a member, and was often victimized by Space Ghost or the other villains. He also co-hosted Cartoon Planet and currently hosts a revival of this series with Zorak.

Voiced by Don Kennedy, Tansit is an overweight and cowardly man in an orange costume and helmet. His outfit makes him appear much more menacing than he actually is, but fails completely at hiding his gut. He replaced Moltar as director of the show twice, and messed it up. His biggest fear is getting zapped by one of Space Ghost's rays. He is a member of the Council of Doom. For about half the episodes of season 4 he announced the show off-screen until he was fired by Space Ghost.

Voiced by Andy Merrill, Lokar is an erudite, giant hominid locust who is prone to violent outbursts and speaks in a British voice. Lokar seems to harbor a grudge towards Space Ghost, and constantly seeks his destruction, perhaps more for his boorishness than anything else. He is also in a long-running feud with Zorak. Lokar is a member of the Council of Doom, though he's not so much evil as a snob. The episode "Pilot" revealed that he was originally going to be the band leader of the show instead of Zorak.

Voiced by Brad Abelle, Chad Ghostal is Space Ghost's evil twin brother, distinguished from Space Ghost in physical appearance only by a crudely drawn Van Dyke beard. He is a beatnik, with a love for jazz music and outdated beatnik slang, and is both extremely cool and evil. He is also quite the ladies' man. Chad first appears in the episode "Switcheroo",[citation needed] where he uses his resemblance to Space Ghost to switch places with him, and again in "Hipster", where he takes over the show after incapacitating Space Ghost.

Voiced by Scott Finnell, Harvey Birdman was the host of the show in the episodes Pilot and Sequel. He also appeared on the side lines during two other episodes. He appears to be washed up, and in a rut, alternately claiming to be unemployed.

Metallus (Michael Tew) - A villain and member of the Council of Doom who can only talk in a reverb-heavy metallic drone, rendering his every word incomprehensible, though other characters seem to understand him. He is a big metal guy with a blue vest and gloves, and he has a helmet with a large, presumably ornamental "wings". Since he can't talk normally, his personality isn't developed all that much.

Black Widow (Judy Tenuta) - A villain who has professed love for Space Ghost, much to the chagrin of the other villains. She is known for her scream that irritates Space Ghost. She also appeared in Johnny Bravo as a guest star.

Raymond (C. Martin Croker) - Zorak's previously unheard-of nephew. Space Ghost immediately took a liking to the cute miniature version of Zorak. Predictably, Raymond was eaten by Zorak before the end of the episode. He made appearances in 2 other episodes.

The Original Way Outs - The show's band, led by Zorak. The show has never explained their origins; in fact, very little attention is paid to them at all.

The Sorcerer - A member of The Original Way Outs with a large flesh-toned head and yellow eyes. He speaks on extremely rare occasions, as alluded to by Space Ghost in the episode Mayonnaise ("When did you start talking?"). His name was revealed on the commentary for the episode Zoltran.

Kristy - the drummer of The Original Way Outs. He never speaks, althoughhe is frequently directly addressed by Space Ghost and Zorak.

Bob (Tom Arcuragi) - Featured in the fourth season, he acts as the shows director telling them what they need to do and how to do it, but he was featured in episodes that take place before the series actually took place and started.